Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with 40,000 new cases and 11,000 deaths occurring each year in the United States. Despite advances that improve the quality of life for patients, there has been little to no improvement in survival for the last 30 years. Among the genetic aberrations that occur in HNSCC, 11q13 amplification is one of the most common and is strongly linked to poor prognosis and decreased survival of patients. A strong candidate gene within that amplicon to promote tumor aggressiveness is cortactin, a cytoskeletal protein that promotes cell motility and invasion. Mechanistically, cortactin is an essential component of invadopodia, cell surface protrusions thought to be involved in cancer invasion; however it is not clear to what extent this activity contributes to tumor growth and aggressiveness in vivo. The goal of our study is to test the individual role of cortactin in progression of 11q13-amplified HNSCC tumors. Through the use of retroviral expression systems to manipulate cortactin expression in non-amplified and 11q13-amplified HNSCC cell lines, we will test the role of cortactin in HNSCC tumor growth and invasion in vivo and invadopodia activity in vitro. By the end of the grant period, we should have determined 1) whether cortactin promotes HNSCC tumor progression and thus represents a good target for treatment; and 2) whether there is a more general link between invadopodia activity and tumor growth. [unreadable] [unreadable] [unreadable]